Randomized, double blind, controlled placebo-phase in trial of low dose phenelzine in the chronic fatigue syndrome

Abstract:

Because of the striking similarity of the clinical manifestations produced by use of the drug reserpine and seen in patients with the chronic fatigue syndrome (CFS), we theorized that CFS was a disorder of reduced central sympathetic drive. Because of the pharmacology of control of this central sympathetic system, we further postulated that CFS symptoms would respond quickly to low dose treatment with a monamine oxidase inhibitor. To test these hypotheses, we designed a randomized, double blind placebo controlled study using phenelzine.

No patient in the trial had a diagnosis of lifetime or current psychiatric disorder and none had depressed mood in the range of clinically depressed patients on a paper and pencil test of depression. Patients in the placebo group received placebo for 6 weeks while those in the drug treatment group were treated in three 2-week segments-placebo, 15 mg phenelzine every other day, and then 15 mg daily. This treatment regimen produced a significant pattern of improvement compared to worsening in 20 self report vehicles of CFS symptoms, illness severity, mood or functional status.

Thus the data support our hypothesis of reduced sympathetic drive, although an alternative hypothesis of pain alleviation is also possible. The study design also allowed us to evaluate patients for a placebo effect: no evidence for this was found, suggesting that CFS is not an illness due to patients’ being overly suggestible.

 

Source: Natelson BH, Cheu J, Pareja J, Ellis SP, Policastro T, Findley TW. Randomized, double blind, controlled placebo-phase in trial of low dose phenelzine in the chronic fatigue syndrome. Psychopharmacology (Berl). 1996 Apr;124(3):226-30. http://www.ncbi.nlm.nih.gov/pubmed/8740043

 

Preliminary determination of a molecular basis of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS/ME) is a debilitating fatigue illness that has an unknown etiology. We studied 20 chronic fatigue syndrome (CFS) patients, who complied with the Oxford and American CDC definitions, and 45 non-CFS subjects.

Participants completed questionnaires, were clinically examined, and had first morning urine specimens collected, which were screened by gas chromatography-mass spectrometry for changes in metabolite excretion.

Multivariate analysis of the urinary metabolite profiles differed significantly in the CFS patients compared to the non-CFS patients (P < 0.004). The CFS patients had increases in aminohydroxy-N-methylpyrrolidine (P < 0.00003, referred to as chronic fatigue symptom urinary marker 1, or CFSUM1), tyrosine (P < 0.02), beta-alanine (P < 0.02), aconitic acid (P < 0.05), and succinic acid (P < 0.05) and reductions in an unidentified urinary metabolite, CFSUM2 (P < 0.0007), alanine (P < 0.005), and glutamic acid (P < 0.02). CFSUM1, beta-alanine, and CFSUM2 were found by discriminant function analysis to be the first, second, and third most important metabolites, respectively for discriminating between CFS and non-CFS subjects.

The abundances of CFSUM1 and beta-alanine were positively correlated with symptom incidence (P < 0.01 and P < 0.001, respectively), symptom severity, core CFS symptoms, and SCL-90-R somatization (P < 0.00001), suggesting a molecular basis for CFS.

 

Source: McGregor NR, Dunstan RH, Zerbes M, Butt HL, Roberts TK, Klineberg IJ. Preliminary determination of a molecular basis of chronic fatigue syndrome. Biochem Mol Med. 1996 Apr;57(2):73-80. http://www.ncbi.nlm.nih.gov/pubmed/8733884

 

Insulin-like growth factor-I (somatomedin C) levels in chronic fatigue syndrome and fibromyalgia

Abstract:

OBJECTIVE: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are similar conditions characterized by substantial fatigue, diffuse myalgias, sleep disturbances and a variety of other symptoms. Many patients with CFS meet strict criteria for FM. Recently, low insulin-like growth factor-I (IGF-I) levels have been demonstrated in patients with FM, suggesting that disruption of the growth hormone-IGF-I axis might explain the link between the muscle pain and poor sleep. Our goal was to determine whether IGF-I levels are decreased in CFS, and whether such findings are restricted to patients with concurrent FM.

METHODS: Radioimmunoassays were used to determine serum concentrations of IGF-I and its binding protein, (IGFBP-3). Subjects were 3 patients seen in a referral clinic for chronic fatigue: 15 patients with CFS, 15 who met criteria for both CFS and FM (CFS-FM), 27 with FM alone; and 15 healthy control (HC) subjects.

RESULTS: Patients and control subjects had similar demographic and clinical characteristics. No significant differences were observed among any of the 3 patient groups and control subjects in the mean concentration of either IGF-I or IGFBP-3. Likewise, the proportion of subjects with values above or below the laboratory’s reference range did not differ for IGF-I or IGFBP-3.

CONCLUSIONS: These findings suggest the disruption of the growth hormone-IGF-I axis previously demonstrated in FM patients is not evident in a referral population of patients with CFS, CFS-FM, or FM.

 

Source: Buchwald D, Umali J, Stene M. Insulin-like growth factor-I (somatomedin C) levels in chronic fatigue syndrome and fibromyalgia. J Rheumatol. 1996 Apr;23(4):739-42. http://www.ncbi.nlm.nih.gov/pubmed/8730136

 

Periodic K-alpha sleep EEG activity and periodic limb movements during sleep: comparisons of clinical features and sleep parameters

Abstract:

The K-alpha sleep electroencephalographic (EEG) phenomenon is characterized by periodic (approximately 20-40 seconds) K-complexes, immediately followed by alpha-EEG activity (7.5-11 Hz) of 0.5- to 5.0-second duration. A group of 14 subjects with the periodic K-alpha anomaly was found to have a similar distribution pattern of interevent intervals as compared with previously published data for sleep-related periodic limb movements during sleep (PLMS). Sleep parameters and somatic symptoms of 30 patients with K-alpha were compared with 30 patients with PLMS. The periodic K-alpha group was predominantly female, younger, exhibiting more slow-wave sleep, gastrointestinal symptoms and muscular complaints and fewer movement arousals on overnight polysomnography. The K-alpha group presented uniformly with complaints of unrefreshing sleep, often associated with fibromyalgia and chronic fatigue syndrome. The PLMS group was predominantly male, showed greater sleep disruption and presented with a variety of sleep-related symptoms.

 

Source: MacFarlane JG, Shahal B, Mously C, Moldofsky H. Periodic K-alpha sleep EEG activity and periodic limb movements during sleep: comparisons of clinical features and sleep parameters. Sleep. 1996 Apr;19(3):200-4. http://www.ncbi.nlm.nih.gov/pubmed/8723376

 

Chronic fatigue syndrome–also an insurance medicine problem

Abstract:

Not everybody who is chronically tired has a chronic fatigue syndrome. The diagnosis of the chronic fatigue syndrome is still a problem, and is becoming a problem in health insurance medicine too. There is a lack of knowledge concerning the causes, the diagnosis and the therapy of the chronic fatigue syndrome. And there is still the question if the chronic fatigue syndrome is an entity of its own. For these reasons we should apply the few facts we really know about the chronic fatigue syndrome. This is the working case definition of Kaplan et al. from 1988. Otherwise there will be done hundreds of expensive laboratory tests, which are useless for the patient and very costly for the health insurance companies.

 

Source: Hakimi R. Chronic fatigue syndrome–also an insurance medicine problem. Versicherungsmedizin. 1996 Apr 1;48(2):59-61. [Article in German] http://www.ncbi.nlm.nih.gov/pubmed/8659056

 

Expert assessment of chronic fatigue syndrome

Abstract:

The Chronic-Fatigue-Syndrome (CFS) has been first described in 1988 and has been also in Germany recently more frequently diagnosed. It is similar to a lot of other terms, especially to “neurasthenia”, which has been introduced 1869 from Beard and is now again content of ICD-10. CFS is defined by primary and secondary criteria, which are however largely subjective. There are no objective signs. It is unknown if this syndrome represents a disease entity of its own. The explanation is either exclusive organic based on immunological and virological findings or exclusive psychogenic as a special form of anxiety psychosis. Possibly are both factors involved as part of “psycho-neuro-immunology”. CFS is increased subject of medical certification. It has been tried to give a practical guidance to the assessment of CFS.

 

Source: Hausotter W. Expert assessment of chronic fatigue syndrome. Versicherungsmedizin. 1996 Apr 1;48(2):57-9. [Article in German] http://www.ncbi.nlm.nih.gov/pubmed/8659055

 

Chronic fatigue syndrome–psychiatric aspects

Abstract:

Diagnosis of the chronic fatigue syndrome depends on various somatic and psychopathological symptoms. Somatic symptoms of the syndrome have been subject of an extensive body of literature. In comparison, psychiatric aspects have caught relatively less attention.

Psychiatric aspects of etiological, diagnostic, and therapeutic concepts are essential for evaluation of the syndrome. Application of CDC-criteria to a well known disease does not solve the nosological problem, but may define the syndrome more accurately. In this respect, issues including psychiatric comorbidity and specificity of neuropathological symptoms are discussed.

Psychological variables seem to have a high predictor value for time course and outcome of the symptoms. Etiological concepts emphasize on biological or psychosocial factors. Alterations of biological parameters including immune functions, sleep regulation, and hypothalamic-pituary-adrenocortical function have been reported. The role of cultural factors has been discussed extensively. Somatic and psychological stress may result in the same clinical syndrome via psychoimmunological mechanisms. An integrated, interdisciplinary approach to further refine diagnostic criteria, understanding of etiology and development of adequate therapeutic measures seems necessary.

 

Source: Lemke MR. Chronic fatigue syndrome–psychiatric aspects. Fortschr Neurol Psychiatr. 1996 Apr;64(4):132-41. [Article in German] http://www.ncbi.nlm.nih.gov/pubmed/8655125

 

Randomised, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome

Abstract:

BACKGROUND: No somatic treatment has been found to be effective for chronic fatigue syndrome (CFS). Antidepressant therapy is commonly used. Fluoxetine is recommended in preference to tricyclic agents because it has fewer sedative and autonomic nervous system effects. However, there have been no randomised, placebo-controlled, double-blind studies showing the effectiveness of antidepressant therapy in CFS. We have carried out such a study to assess the effect of fluoxetine in depressed and non-depressed CFS patients.

METHODS: In this randomised, double-blind study, we recruited 44 patients to the depressed CFS group, and 52 to the non-depressed CFS group. In each group participants were randomly assigned to receive either fluoxetine (20 mg once daily) or placebo for 8 weeks. The effect of fluoxetine was assessed by questionnaires, self-observation lists, standard neuropsychological tests, and a motion-sensing device (Actometer), which were applied on the day treatment started and on the last day.

FINDINGS: The two groups were well matched in terms of age, sex distribution, employment and marital status, and duration of CFS. There were no significant differences between the placebo and fluoxetine-treated groups in the change during the 8-week treatment period for any dimension of CFS. There was no change in subjective assessments of fatigue, severity of depression, functional impairment, sleep disturbances, neuropsychological function, cognitions, or physical activity in the depressed or the non-depressed subgroup.

INTERPRETATION: Fluoxetine in a 20 mg daily dose does not have a beneficial effect on any characteristic of CFS. The lack of effect of fluoxetine on depressive symptoms in CFS suggests that processes underlying the presentation of depressive symptoms in CFS may differ from those in patients with major depressive disorder.

 

Source: Vercoulen JH, Swanink CM, Zitman FG, Vreden SG, Hoofs MP, Fennis JF, Galama JM, van der Meer JW, Bleijenberg G. Randomised, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome. Lancet. 1996 Mar 30;347(9005):858-61. http://www.ncbi.nlm.nih.gov/pubmed/8622391

 

Neurocognitive functioning in chronic fatigue syndrome

Abstract:

Although substantial research has been conducted on chronic fatigue syndrome (CFS) over the past decade, the syndrome remains poorly understood. The most recent case definition describes CFS as being characterized both by disabling fatigue and by subjective reports of difficulty with concentration and “short-term” memory. However, research into the neurocognitive and psychological functioning of individuals with CFS has provided mixed objective results. The current paper reviews studies that have examined the neurocognitive and/or psychological functioning of individuals with CFS. Changes in research design and instruments employed to study individuals with CFS are suggested.

 

Source: DiPino RK, Kane RL. Neurocognitive functioning in chronic fatigue syndrome. Neuropsychol Rev. 1996 Mar;6(1):47-60. http://www.ncbi.nlm.nih.gov/pubmed/9144668

 

Screening for psychiatric morbidity in subjects presenting with chronic fatigue syndrome

Abstract:

BACKGROUND: There is a need for a valid self-rating questionnaire to screen for psychiatric morbidity in patients with chronic fatigue syndrome (CFS). This study had the aim of assessing the utility and validity of two commonly used measures.

METHOD: Scores obtained on the General Health Questionnaire (GHQ) and the Beck Depression Inventory (BDI) were compared with various diagnostic and severity ratings obtained via a validating clinical interview, the Schedules for the Clinical Assessment of Neuropsychiatry (SCAN) in 95 consecutively referred subjects at a medical out-patient clinic who fulfilled standard criteria for CFS, and 48 healthy controls. Outcome measures were validating coefficients and receiver operating characteristics (ROC) for different thresholds and scoring on GHQ and BDI and index of definition (ID) as measured by SCAN; and Pearson and point by serial correlation coefficients for different diagnostic groups derived via SCAN and defined according to ICD-10 and DSM-III-R.

RESULTS: GHQ and BDI perform poorly as screeners of psychiatric morbidity in CFS subjects when compared with various SCAN derived ratings although results for controls are comparable with other studies.

CONCLUSIONS: Neither the GHQ nor BDI alone can be recommended as screeners for psychiatric morbidity in CFS subjects.

 

Source: Farmer A, Chubb H, Jones I, Hillier J, Smith A, Borysiewicz L. Screening for psychiatric morbidity in subjects presenting with chronic fatigue syndrome. Br J Psychiatry. 1996 Mar;168(3):354-8. http://www.ncbi.nlm.nih.gov/pubmed/8833692